The 2017 International League Against Epilepsy classification has defined a three‐tier system with epilepsy syndrome identification at the third level. Although a syndrome cannot be determined in all children with epilepsy, identification of a specific syndrome provides guidance on management and prognosis. In this paper, we describe the childhood onset epilepsy syndromes, most of which have both mandatory seizure type(s) and interictal electroencephalographic (EEG) features. Based on the 2017 Classification of Seizures and Epilepsies, some syndrome names have been updated using terms directly describing the seizure semiology. Epilepsy syndromes beginning in childhood have been divided into three categories: (1) self‐limited focal epilepsies, comprising four syndromes: self‐limited epilepsy with centrotemporal spikes, self‐limited epilepsy with autonomic seizures, childhood occipital visual epilepsy, and photosensitive occipital lobe epilepsy; (2) generalized epilepsies, comprising three syndromes: childhood absence epilepsy, epilepsy with myoclonic absence, and epilepsy with eyelid myoclonia; and (3) developmental and/or epileptic encephalopathies, comprising five syndromes: epilepsy with myoclonic–atonic seizures, Lennox–Gastaut syndrome, developmental and/or epileptic encephalopathy with spike‐and‐wave activation in sleep, hemiconvulsion–hemiplegia–epilepsy syndrome, and febrile infection‐related epilepsy syndrome. We define each, highlighting the mandatory seizure(s), EEG features, phenotypic variations, and findings from key investigations.

The International League Against Epilepsy (ILAE) Task Force on Nosology and Definitions proposes a classification and definition of epilepsy syndromes in the neonate and infant with seizure onset up to 2 years of age. The incidence of epilepsy is high in this age group and epilepsy is frequently associated with significant comorbidities and mortality. The licensing of syndrome specific antiseizure medications following randomized controlled trials and the development of precision, gene‐related therapies are two of the drivers defining the electroclinical phenotypes of syndromes with onset in infancy. The principal aim of this proposal, consistent with the 2017 ILAE Classification of the Epilepsies, is to support epilepsy diagnosis and emphasize the importance of classifying epilepsy in an individual both by syndrome and etiology. For each syndrome, we report epidemiology, clinical course, seizure types, electroencephalography (EEG), neuroimaging, genetics, and differential diagnosis. Syndromes are separated into self‐limited syndromes, where there is likely to be spontaneous remission anddevelopmental and epileptic encephalopathies, diseases where there is developmental impairment related to both the underlying etiology independent of epileptiform activity and the epileptic encephalopathy. The emerging class of etiology‐specific epilepsy syndromes, where there is a specific etiology for the epilepsy that is associated with a clearly defined, relatively uniform, and distinct clinical phenotype in most affected individuals as well as consistent EEG, neuroimaging, and/or genetic correlates, is presented. The number of etiology‐defined syndromes will continue to increase, and these newly described syndromes will in time be incorporated into this classification. The tables summarize mandatory features, cautionary alerts, and exclusionary features for the common syndromes. Guidance is given on the criteria for syndrome diagnosis in resource‐limited regions where laboratory confirmation, including EEG, MRI, and genetic testing, might not be available.

Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Na_v1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71 patients and review 130 previously reported patients. We found that (i) encephalopathies with infantile/childhood onset epilepsies (≥3 months of age) occur almost as often as those with an early infantile onset (<3 months), and are thus more frequent than previously reported; (ii) distinct phenotypes can be seen within the late onset group, including myoclonic-atonic epilepsy (two patients), Lennox-Gastaut not emerging from West syndrome (two patients), and focal epilepsies with an electrical status epilepticus during slow sleep-like EEG pattern (six patients); and (iii) West syndrome constitutes a common phenotype with a major recurring mutation (p.Arg853Gln: two new and four previously reported children). Other known phenotypes include Ohtahara syndrome, epilepsy of infancy with migrating focal seizures, and intellectual disability or autism without epilepsy. To assess the response to antiepileptic therapy, we retrospectively reviewed the treatment regimen and the course of the epilepsy in 66 patients for which well-documented medical information was available. We find that the use of sodium channel blockers was often associated with clinically relevant seizure reduction or seizure freedom in children with early infantile epilepsies (<3 months), whereas other antiepileptic drugs were less effective. In contrast, sodium channel blockers were rarely effective in epilepsies with later onset (≥3 months) and sometimes induced seizure worsening. Regarding the genetic findings, truncating mutations were exclusively seen in patients with late onset epilepsies and lack of response to sodium channel blockers. Functional characterization of four selected missense mutations using whole cell patch-clamping in tsA201 cells—together with data from the literature—suggest that mutations associated with early infantile epilepsy result in increased sodium channel activity with gain-of-function, characterized by slowing of fast inactivation, acceleration of its recovery or increased persistent sodium current. Further, a good response to sodium channel blockers clinically was found to be associated with a relatively small gain-of-function. In contrast, mutations in patients with late-onset forms and an insufficient response to sodium channel blockers were associated with loss-of-function effects, including a depolarizing shift of voltage-dependent activation or a hyperpolarizing shift of channel availability (steady-state inactivation). Our clinical and experimental data suggest a correlation between age at disease onset, response to sodium channel blockers and the functional properties of mutations in children with SCN2A-related epilepsy.

In 2017, the International League Against Epilepsy (ILAE) Classification of Epilepsies described the “genetic generalized epilepsies” (GGEs), which contained the “idiopathic generalized epilepsies” (IGEs). The goal of this paper is to delineate the four syndromes comprising the IGEs, namely childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and epilepsy with generalized tonic–clonic seizures alone. We provide updated diagnostic criteria for these IGE syndromes determined by the expert consensus opinion of the ILAE’s Task Force on Nosology and Definitions (2017–2021) and international external experts outside our Task Force. We incorporate current knowledge from recent advances in genetic, imaging, and electroencephalographic studies, together with current terminology and classification of seizures and epilepsies. Patients that do not fulfill criteria for one of these syndromes, but that have one, or a combination, of the following generalized seizure types: absence, myoclonic, tonic‐clonic and myoclonic‐tonic‐clonic seizures, with 2.5–5.5 Hz generalized spike‐wave should be classified as having GGE. Recognizing these four IGE syndromes as a special grouping among the GGEs is helpful, as they carry prognostic and therapeutic implications.

The International League Against Epilepsy (ILAE) has updated the operational classification of epileptic seizures, building upon the framework established in 2017. This revision, informed by the implementation experience, involved a working group appointed by the ILAE Executive Committee. Comprising 37 members from all ILAE regions, the group utilized a modified Delphi process, requiring a consensus threshold of more than two thirds for any proposal. Following public comments, the Executive Committee appointed seven additional experts to the revision task force to address and incorporate the issues raised, as appropriate. The updated classification maintains four main seizure classes: Focal, Generalized, Unknown (whether focal or generalized), and Unclassified. Taxonomic rules distinguish classifiers, which are considered to reflect biological classes and directly impact clinical management, from descriptors, which indicate other important seizure characteristics. Focal seizures and those of unknown origin are further classified by the patient's state of consciousness (impaired or preserved) during the seizure, defined operationally through clinical assessment of awareness and responsiveness. If the state of consciousness is undetermined, the seizure is classified under the parent term, that is, the main seizure class (focal seizure or seizure of unknown origin). Generalized seizures are grouped into absence seizures, generalized tonic–clonic seizures, and other generalized seizures, now including recognition of negative myoclonus as a seizure type. Seizures are described in the basic version as with or without observable manifestations, whereas an expanded version utilizes the chronological sequence of seizure semiology. This updated classification comprises four main classes and 21 seizure types. Special emphasis was placed on ensuring translatability into languages beyond English. Its aim is to establish a common language for all health care professionals involved in epilepsy care, from resource‐limited areas to highly specialized centers, and to provide accessible terms for patients and caregivers.